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Spandana Rajendra Kopalli,Kyu-Min Cha,황석연,Min-Sik Jeong,김시관 고려인삼학회 2019 Journal of Ginseng Research Vol.43 No.1
Background: Panax ginseng Meyer, known as Korean Red Ginseng (KRG), is one of the important age-old traditional herbs used in boosting libido and improving male fertility. In this study, the effects of Rg3- enriched KRG extract (KGC04P) on heat stresseinduced testicular damage in experimental rats was evaluated. Methods: Male rats (Sprague-Dawley) were divided into four groups (n ¼ 10): normal control (NC), heatstressed control (HC), heat-stressed plus KGC04P-100 mg/kg (HK100), and heat-stressed plus KGC04P- 200 mg/kg (HK200) groups. Starting 1 week prior to heat stress, animals were administered orally with KGC04P (100 and 200 mg/kg) mixed with a regular pellet diet and continued for 25 weeks. Heat stress was induced to HC, HK100, and HK200 groups by intermittently exposing the animals to high temperatures (32 1C, 2 h/day). After 6 months, animals were euthanized under general anesthesia with carbon dioxide and evaluated for various parameters in serum and testicular tissue by using Western blotting, biochemical kits, and reverse transcription-polymerase chain reaction. Results: Significant (p < 0.05) alterations in several parameters, such as body/organ weight, sperm kinematics, and lipid metabolism marker levels, in the serum and testis of rats were observed. Further, the expression of testicular antioxidant enzymes, inflammatory cytokines, sex hormonal receptors, and spermatogenesis-related genes were also affected significantly (p < 0.05) in the heat-stressed group. However, KGC04P prevented the heat stresseinduced changes in rats significantly (p < 0.05) at both concentrations. Conclusion: KGC04P attenuated heat stresseinduced testicular damage by a multifunctional approach and can be developed as an excellent therapeutic agent for hyperthermia-mediated male infertility.
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Spandana Rajendra Kopalli,Kyu-Min Cha,Seock-Yeon Hwang,Min-Sik Jeong,Si-Kwan Kim 고려인삼학회 2019 Journal of Ginseng Research Vol.43 No.1
Background: Panax ginseng Meyer, known as Korean Red Ginseng (KRG), is one of the important age-old traditional herbs used in boosting libido and improving male fertility. In this study, the effects of Rg3- enriched KRG extract (KGC04P) on heat stress-induced testicular damage in experimental rats was evaluated. Methods: Male rats (Sprague-Dawley) were divided into four groups (n=10): normal control (NC), heat-stressed control (HC), heat-stressed plus KGC04P-100 mg/kg (HK100), and heat-stressed plus KGC04P-200 mg/kg (HK200) groups. Starting 1 week prior to heat stress, animals were administered orally with KGC04P (100 and 200 mg/kg) mixed with a regular pellet diet and continued for 25 weeks. Heat stress was induced to HC, HK100, and HK200 groups by intermittently exposing the animals to high temperatures (32 ±1℃, 2 h/day). After 6 months, animals were euthanized under general anesthesia with carbon dioxide and evaluated for various parameters in serum and testicular tissue by using Western blotting, biochemical kits, and reverse transcription-polymerase chain reaction. Results: Significant (p < 0.05) alterations in several parameters, such as body/organ weight, sperm kinematics, and lipid metabolism marker levels, in the serum and testis of rats were observed. Further, the expression of testicular antioxidant enzymes, inflammatory cytokines, sex hormonal receptors, and spermatogenesis-related genes were also affected significantly (p < 0.05) in the heat-stressed group. However, KGC04P prevented the heat stress-induced changes in rats significantly (p < 0.05) at both concentrations. Conclusion: KGC04P attenuated heat stress-induced testicular damage by a multifunctional approach and can be developed as an excellent therapeutic agent for hyperthermia-mediated male infertility.
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Spandana Rajendra Kopalli,Kyu-Min Cha,Sang-Ho Lee,Ji-Hoon Ryu,Seock-Yeon Hwang,Min-Sik Jeong,Jong-Hwan Sung,Si-Kwan Kim 고려인삼학회 2017 Journal of Ginseng Research Vol.41 No.4
Background: Elevated testicular temperature disrupts spermatogenesis and causes infertility. In the present study, the protective effect of enzymatically biotransformed Panax ginseng Meyer by pectinase (GINST) against chronic intermittent heat stress-induced testicular damage in rats was investigated. Methods: Male SpragueeDawley rats (4 wk old, 60e70 g) were divided into four groups: normal control (NC), heat-stress control (HC), heat-stress plus GINST-100 mg/kg (HG100), and heat-stress plus GINST-200 mg/kg (HG200) treatment groups. Each dose of GINST (100 mg/kg and 200 mg/kg) was mixed separately with a regular pellet diet and was administered orally for 24 wk. For inducing heat stress, rats in the NC group were maintained at 25℃, whereas rats in the HC, HG100, and HG200 groups were exposed to 32 ±1℃ for 2 h daily for 6 mo. At week 25, the testes and serum from each animal were analyzed for various parameters. Results: Significant (p < 0.01) changes in the sperm kinematic values and blood chemistry panels were observed in the HC group. Furthermore, spermatogenesis-related molecules, sex hormone receptors, and selected antioxidant enzyme expression levels were also altered in the HC group compared to those in the NC group. GINST (HS100 and HS200) administration significantly (p < 0.05) restored these changes when compared with the HC group. For most of the parameters tested, the HG200 group exhibited potent effects compared with those exhibited by the HG100 group. Conclusion: GINST may be categorized as an important medicinal herb and a potential therapeutic for the treatment of male subfertility or infertility caused by hyperthermia.
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Spandana Rajendra Kopalli,차규민,Konkuk University,Sang-Ho Lee,Jong-Hwan Sung,Seok-Kyo Seo,Si-Kwan Kim 고려인삼학회 2016 Journal of Ginseng Research Vol.40 No.2
Background: To investigate the effect of pectinase-treated Panax ginseng (GINST) in cellular and male subfertility animal models. Methods: Hydrogen peroxide (H2O2)-induced mouse spermatocyte GC-2spd cells were used as an in vitro model. Cell viability was measured using MTT assay. For the in vivo study, GINST (200 mg/kg) mixed with a regular pellet diet was administered orally for 4 mo, and the changes in the mRNA and protein expression level of antioxidative and spermatogenic genes in young and aged control rats were compared using real-time reverse transcription polymerase chain reaction and western blotting. Results: GINST treatment (50 mg/mL, 100 mg/mL, and 200 mg/mL) significantly (p < 0.05) inhibited the H2O2-induced (200 mM) cytotoxicity in GC-2spd cells. Furthermore, GINST (50 mg/mL and 100 mg/mL) significantly (p < 0.05) ameliorated the H2O2-induced decrease in the expression level of antioxidant enzymes (peroxiredoxin 3 and 4, glutathione S-transferase m5, and glutathione peroxidase 4), spermatogenesis-related protein such as inhibin-a, and specific sex hormone receptors (androgen receptor, luteinizing hormone receptor, and follicle-stimulating hormone receptor) in GC-2spd cells. Similarly, the altered expression level of the above mentioned genes and of spermatogenesis-related nectin-2 and cAMP response element-binding protein in aged rat testes was ameliorated with GINST (200 mg/kg) treatment. Taken together, GINST attenuated H2O2-induced oxidative stress in GC-2 cells and modulated the expression of antioxidant-related genes and of spermatogenic-related proteins and sex hormone receptors in aged rats. Conclusion: GINST may be a potential natural agent for the protection against or treatment of oxidative stress-induced male subfertility and aging-induced male subfertility.
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Kopalli, Spandana Rajendra,Cha, Kyu-Min,Ryu, Ji-Hoon,Lee, Sang-Ho,Jeong, Min-Sik,Hwang, Seock-Yeon,Lee, Young-Joo,Song, Hee-Won,Kim, Su-Nam,Kim, Jin-Chul,Kim, Si-Kwan Elsevier 2017 Experimental Gerontology Vol.90 No.-
<P><B>Abstract</B></P> <P>Korean red ginseng (<I>Panax ginseng</I> Meyer) is known to rejuvenate testicular effectiveness and the sperm maturation process by regulating redox proteins in aged rats. This study was performed to investigate the effect of Korean red ginseng water extract (KRG-WE) on the expression level of spermatogenesis-related key biomolecules and sex hormone receptors as well as enzymes regulating oxidation, histone deacetylation, and growth-related activities in aged rat testis. KRG-WE (200mg/kg) mixed with a regular pellet diet was administered to 12-month-old rats for 6months (KRG-AC), whereas the young (YC, 2months) and aged (AC, 12months) controls received the vehicle only. The results showed that the expression levels of spermatogenesis-related key biomolecules (inhibin-α, nectin-2, and cyclic adenosine monophosphate [cAMP] responsive element binding protein [CREB]-1), sex hormone receptors (androgen, luteinizing- and follicle-stimulating hormone receptors [AR, LHR, and FSHR, respectively]), and antioxidant enzymes (glutathione <I>S</I>-transferase mu [GSTm]-5, glutathione peroxidase [GPx]-4, peroxiredoxin [PRx]-3), as well as histone deactylation (silent mating type information regulation 2 homolog 1, SIRT1) and growth-related (mammalian target of rapamycin complex 1, mTORC1) molecules were significantly altered in the AC group rat testes compared with those of the YC group. However, KRG-WE treatment of the AC group significantly (<I>p</I> <0.05) attenuated these molecular changes. From these results, it can be concluded that long-term administration of KRG-WE significantly delayed the aging-induced testicular dysfunction.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Korean red ginseng (KRG) improves testicular dysfunction in aged rats. </LI> <LI> KRG attenuated the altered expression levels of sex hormone receptors in aged rats. </LI> <LI> KRG restored the expression of antioxidant enzyme status in aged rats. </LI> <LI> KRG attenuates the aging-induced changes in spermatogenesis-related molecules. </LI> </UL> </P>
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Kopalli, Spandana Rajendra,Cha, Kyu-Min,Hwang, Seock-Yeon,Jeong, Min-Sik,Kim, Si-Kwan The Korean Society of Ginseng 2019 Journal of Ginseng Research Vol.43 No.1
Background: Panax ginseng Meyer, known as Korean Red Ginseng (KRG), is one of the important age-old traditional herbs used in boosting libido and improving male fertility. In this study, the effects of Rg3-enriched KRG extract (KGC04P) on heat stress-induced testicular damage in experimental rats was evaluated. Methods: Male rats (Sprague-Dawley) were divided into four groups (n = 10): normal control (NC), heat-stressed control (HC), heat-stressed plus KGC04P-100 mg/kg (HK100), and heat-stressed plus KGC04P-200 mg/kg (HK200) groups. Starting 1 week prior to heat stress, animals were administered orally with KGC04P (100 and 200 mg/kg) mixed with a regular pellet diet and continued for 25 weeks. Heat stress was induced to HC, HK100, and HK200 groups by intermittently exposing the animals to high temperatures ($32{\pm}1^{\circ}C$, 2 h/day). After 6 months, animals were euthanized under general anesthesia with carbon dioxide and evaluated for various parameters in serum and testicular tissue by using Western blotting, biochemical kits, and reverse transcription-polymerase chain reaction. Results: Significant (p < 0.05) alterations in several parameters, such as body/organ weight, sperm kinematics, and lipid metabolism marker levels, in the serum and testis of rats were observed. Further, the expression of testicular antioxidant enzymes, inflammatory cytokines, sex hormonal receptors, and spermatogenesis-related genes were also affected significantly (p < 0.05) in the heat-stressed group. However, KGC04P prevented the heat stress-induced changes in rats significantly (p < 0.05) at both concentrations. Conclusion: KGC04P attenuated heat stress-induced testicular damage by a multifunctional approach and can be developed as an excellent therapeutic agent for hyperthermia-mediated male infertility.
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Kopalli, Spandana Rajendra,Cha, Kyu-Min,Ryu, Ji-Hoon,Hwang, Seock-Yeon,Kim, Si-Kwan ELSEVIER SCIENCE B.V.; AMSTERDAM 2017 JOURNAL OF FUNCTIONAL FOODS Vol.29 No.-
<P><B>Abstract</B></P> <P>Korean red ginseng (<I>Panax ginseng</I> Meyer, KRG) is a functional food with multiple therapeutic benefits. This study evaluated the fraction-specific effects of KRG in ageing-induced testicular dysfunction rat model. KRG water extract (KRG-WE; 200mg/kg), crude saponin (CS; 20mg/kg), and non-saponin (NS; 180mg/kg) fractions were administered orally for six months. Body weight increments, blood chemistry, histological parameters, sperm kinematics, expression levels of key spermatogenesis molecules and anti-oxidative enzyme status were determined in vehicle treated young and aged control groups. KRG-WE, CS and NS fractions significantly (<I>p</I> <0.05) ameliorated the ageing-induced testicular damage in all the parameters tested. Although total KRG-WE outperformed the tested activities, both CS and NS fractions also exhibited distinct effects in improving ageing-induced testicular dysfunction in rats. The potential non-saponin active constituents in combination with CS fraction might be responsible for such synergistic effect. More detailed study on the KRG-NS fraction active constituents is quite essential.</P> <P><B>Highlights</B></P> <P> <UL> <LI> KRG fractions attenuated ageing-induced rat testicular dysfunction. </LI> <LI> KRG fractions enhanced the antioxidant status in aged rat testes. </LI> <LI> KRG fractions regulated sex hormonal receptor expression aged rat testes. </LI> <LI> KRG and its fractions showed distinctive beneficial effects. </LI> </UL> </P>
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Kopalli, Spandana Rajendra,Cha, Kyu-Min,Lee, Sang-Ho,Ryu, Ji-Hoon,Hwang, Seock-Yeon,Jeong, Min-Sik,Sung, Jong-Hwan,Kim, Si-Kwan The Korean Society of Ginseng 2017 Journal of Ginseng Research Vol.41 No.4
Background: Elevated testicular temperature disrupts spermatogenesis and causes infertility. In the present study, the protective effect of enzymatically biotransformed Panax ginseng Meyer by pectinase (GINST) against chronic intermittent heat stress-induced testicular damage in rats was investigated. Methods: Male Sprague-Dawley rats (4 wk old, 60-70 g) were divided into four groups: normal control (NC), heat-stress control (HC), heat-stress plus GINST-100 mg/kg (HG100), and heat-stress plus GINST-200 mg/kg (HG200) treatment groups. Each dose of GINST (100 mg/kg and 200 mg/kg) was mixed separately with a regular pellet diet and was administered orally for 24 wk. For inducing heat stress, rats in the NC group were maintained at $25^{\circ}C$, whereas rats in the HC, HG100, and HG200 groups were exposed to $32{\pm}1^{\circ}C$ for 2 h daily for 6 mo. At week 25, the testes and serum from each animal were analyzed for various parameters. Results: Significant (p < 0.01) changes in the sperm kinematic values and blood chemistry panels were observed in the HC group. Furthermore, spermatogenesis-related molecules, sex hormone receptors, and selected antioxidant enzyme expression levels were also altered in the HC group compared to those in the NC group. GINST (HS100 and HS200) administration significantly (p < 0.05) restored these changes when compared with the HC group. For most of the parameters tested, the HG200 group exhibited potent effects compared with those exhibited by the HG100 group. Conclusion: GINST may be categorized as an important medicinal herb and a potential therapeutic for the treatment of male subfertility or infertility caused by hyperthermia.
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Kopalli Spandana Rajendra,Cha Kyu-Min,Cho Jae Youl,Kim Si-Kwan,Koppula Sushruta 한국균학회 2022 Mycobiology Vol.50 No.1
Inflammaging in male reproductive organs covers a wide variety of problems, including sex- ual dysfunction and infertility. In this study, the beneficial effects of cordycepin (COR), iso- lated from potential medicinal fungi Cordyceps militaris, in aging-associated testicular inflammation and serum biochemical changes in naturally aged rats were investigated. Male Sprague Dawley rats were divided into young control (YC), aged control (AC), and COR (5, 10, and 20 mg/kg) treated aged rat groups. Aging-associated serum biochemical changes and inflammatory parameters were analyzed by biochemical assay kits, Western blotting, and real-time RT-PCR. Results showed a significant (p < 0.05) alteration in the total blood cell count, lipid metabolism, and liver functional parameters in AC group when compared with YC group. However, COR-treated aged rats ameliorated the altered biochemical parameters significantly (p < 0.05 and p < 0.01 at 5, 10, and 20 mg/kg, respectively). Furthermore, the increase in the expression of inflammatory mediators (COX-2, interleukin (IL)-6, IL-1b, and tis- sue necrosis factor-alpha) in aged rat testis was significant (p < 0.05) when compared with YC group. Treatment with COR at 20 mg/kg to aged rats attenuated the increased expression of inflammatory mediators significantly (p < 0.05). Mechanistic studies revealed that the potential attenuating effects exhibited by COR in aged rats was mediated by regulation of NF-jB activation and MAPKs (c-Jun N-terminal kinase, extracellular signal-regulated kinase 1/ 2, and p38) signaling. In conclusion, COR restored the altered serum biochemical parameters in aged rats and ameliorated the aging-associated testicular inflammation proving the thera- peutic benefits of COR targeting inflammaging-associated male sexual dysfunctions.
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Kopalli, Spandana Rajendra,Cha, Kyu-Min,Jeong, Min-Sik,Lee, Sang-Ho,Sung, Jong-Hwan,Seo, Seok-Kyo,Kim, Si-Kwan The Korean Society of Ginseng 2016 Journal of Ginseng Research Vol.40 No.2
Background: To investigate the effect of pectinase-treated Panax ginseng (GINST) in cellular and male subfertility animal models. Methods: Hydrogen peroxide ($H_2O_2$)-induced mouse spermatocyte GC-2spd cells were used as an in vitro model. Cell viability was measured using MTT assay. For the in vivo study, GINST (200 mg/kg) mixed with a regular pellet diet was administered orally for 4 mo, and the changes in the mRNA and protein expression level of antioxidative and spermatogenic genes in young and aged control rats were compared using real-time reverse transcription polymerase chain reaction and western blotting. Results: GINST treatment ($50{\mu}g/mL$, $100{\mu}g/mL$, and $200{\mu}g/mL$) significantly (p < 0.05) inhibited the $H_2O_2$-induced ($200{\mu}M$) cytotoxicity in GC-2spd cells. Furthermore, GINST ($50{\mu}g/mL$ and $100{\mu}g/mL$) significantly (p < 0.05) ameliorated the $H_2O_2$-induced decrease in the expression level of antioxidant enzymes (peroxiredoxin 3 and 4, glutathione S-transferase m5, and glutathione peroxidase 4), spermatogenesis-related protein such as inhibin-${\alpha}$, and specific sex hormone receptors (androgen receptor, luteinizing hormone receptor, and follicle-stimulating hormone receptor) in GC-2spd cells. Similarly, the altered expression level of the above mentioned genes and of spermatogenesis-related nectin-2 and cAMP response element-binding protein in aged rat testes was ameliorated with GINST (200 mg/kg) treatment. Taken together, GINST attenuated $H_2O_2$-induced oxidative stress in GC-2 cells and modulated the expression of antioxidant-related genes and of spermatogenic-related proteins and sex hormone receptors in aged rats. Conclusion: GINST may be a potential natural agent for the protection against or treatment of oxidative stress-induced male subfertility and aging-induced male subfertility.
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